UC San Diego

This dissertation explores the overarching question of how the Toll signaling pathway mediates Drosophila defense against pathogens. I first discuss my research in collaboration with Scott Lindsay on the Bomanins, a family of Toll-induced secreted peptides required for Toll- mediated defense. We demonstrated that high expression of short-form Bomanins is required for humoral defense against Candida glabrata infection and determined that the Bomanins do not affect the presence or processing of two antimicrobial peptides (AMPs).

The second half investigates the function of a previously uncharacterized Toll effector, Bombardier. I demonstrated that Bombardier is required for defense against fungi and Gram-positive bacteria, and that deletion of bombardier results in the specific absence of short-form Bomanins from hemolymph. Furthermore, flies lacking Bombardier exhibited a defect in pathogen tolerance linked to aberrant Toll activation, specifically from expression of Bomanins. These results suggest a model in which the presence of Bombardier enables secretion or intermolecular associations of short-form Bomanins, and the absence of Bombardier disrupts these steps, resulting in defects in both immune resistance and tolerance.

It has been previously thought that AMPs, some of which are conserved throughout eukaryotes, are the primary effectors of innate immunity. However, recent research in Drosophila has shown that AMPs play a relatively minor role in Toll-mediated immune defense. Supporting these findings, this dissertation finds that Bomanins and Bombardier, which are Drosophila-specific proteins, are vital for Toll-mediated immune defense in an AMP-independent manner, and encourages further exploration into genus-specific proteins.